Jenifer was born in 1723 of Swedish and English descent at Coates Retirement (now Ellerslie) estate, near Port Tobacco in Charles County, Maryland. Little is known about his childhood or education, but as an adult he came into possession of a large estate near Annapolis, called Stepney, where he lived most of his life. He never married. The web of his far-reaching friendships included such illustrious personages as George Washington.
As a young man, Jenifer served as agent and receiver-general for the last two proprietors of Maryland. He also filled the post of justice of the peace in Charles County and later for the western circuit of Maryland. In 1760 he sat on a boundary commission that settled disputes between Pennsylvania and Delaware. Six years later, he became a member of the provincial court and from 1773 to 1776 sat on the Maryland royal governor's council.
Despite his association with conservative proprietary politics, Jenifer supported the Revolutionary movement, albeit at first reluctantly. He served as president of the Maryland council of safety (1775-77), then as president of the first state senate (1777-80). He sat in the Continental Congress (1778-82) and held the position of state revenue and financial manager (1782-85).
A conservative nationalist, Jenifer favored a strong and permanent union of the states and a Congress with taxation power. In 1785 he represented Maryland at the Mount Vernon Conference. Although he was one of 29 delegates who attended nearly every session of the Constitutional Convention, he did not speak often but backed Madison and the nationalist element.
Jenifer lived only 3 more years and never again held public office. He died at the age of 66 or 67 at Annapolis in 1790. The exact location of his grave, possibly at Ellerslie estate, is unknown.